Target-Directed Design, Synthesis, Antiviral Activity, and SARs of 9-Substituted Phenanthroindolizidine Alkaloid Derivatives

On the basis of our previous studies on the antiviral mechanism against tobacco mosaic virus (TMV) and structure-activity relationship of phenanthroindolizidine alkaloids, a series of 9-substituted tylophorine derivatives targeting TMV RNA were designed, synthesized, and assessed for their anti-TMV activities. The bioassay results indicated that most of these compounds showed good in vivo anti-TMV activities, and some of them displayed higher activity than that of commercial ribavirin. Especially, the anti-TMV activities of compound 3b, 4, and 6 are 2-3 times higher than that of commercial ribavirin, according to EC50 values. In this work, we have demonstrated an effective way to design new inhibitors against plant virus and developed 9-ethoxy methyl tylophorine (4) with excellent anti-TMV activity (in vitro activity, 70.2%/500 mu g/mL and 27.1%/100 mu g/mL; inactivation activity, 67.7%/500 mu g/mL and 30.5%/100 mu g/mL; curative activity, 65.3%/500 mu g/mL and 30.8%/100 mu g/mL; and protection activity, 65.9%/500 mu g/mL and 36.0%/100 mu g/mL) as a potential plant viral inhibitor.

Automated summary

A series of 9-substituted tylophorine derivatives targeting TMV RNA were designed, synthesized, and assessed for their anti-TMV activities, with some compounds showing even higher activity than commercial ribavirin. Specifically, compound 3b, 4, and 6 demonstrated 2-3 times higher anti-TMV activities than ribavirin, and compound 4 was identified as a potential plant viral inhibitor with excellent in vitro activity.